A whole series of medical complications of drug abuse have been observed, often summarized in the term psychotoxicity (Seevers), but including psychic as well as somatic effects; there is also over-dosage, leading to acute toxic states and necessitating emergency measures to prevent a lethal outcome. Two main groups of complications will be considered in this survey, viz., psychic complications of abuse of stimulant drugs, mainly phenmetrazine, and two somatic complications of drug abuse by injection, viz., sepsis and infectious hepatitis.

PSYCHIATRIC COMPLICATIONS OF PHENMETRAZINE ABUSE

During the last few years a rapidly increasing number of abusers of stimulant drugs, mainly phenmetrazine, has been noted among individuals arrested for criminal acts by the police, or examined for diagnostic purposes, or treated in the Clinic for Forensic Psychiatry in Stockholm.

Overt psychoses in phenmetrazine abusers were soon observed of a type similar to those which had earlier been described only in amphetamine abusers. A thorough study was therefore begun of all cases of drug abuse among arrested individuals examined at the Forensic Psychiatry Clinic, with the aim to study possible typical effects of chronic intake of high doses of phenmetrazine (Rylander 1966). The importance of having a description of the psychic complications of prolonged phenmetrazine abuse necessitates a more detailed account of this work in the present survey.

Material

The material consisted of 75 systematically examined phenmetrazine abusers, treated at the Clinic during one year, 1 October 1965- 1 October 1966; there were also 75 other phenmetrazine abusers, examined for forensic psychiatric reasons or treated at the Clinic, but not systematically studied in the same thorough way as the first 75, thus making a total of 150 patients.

The total number of drug abusers at the Clinic was 25 in 1964, increasing to 74 in 1966, or increasing from 7.5 to 25.1 per cent of all the patients in the Clinic (table 15).

TABLE 15

Drug abuse among cases at the Clinic for Forensic Psychiatry in Stockholm 1964-1966

Drug abuse

Types of drugs abused

Year

Total number of cases

Opiates

Cann.

Stimulants

Halluc. (LSD)

Hypn. tranq.

total number of drug abusers

Per cent of total number of cases

1964

333

2

20 (18)

3

25

7.5

1965

315

5

45 (44)

4

54

17.1

1966

295

9

3

59 (51)

2

1

74

25.1

Total

16

3

124 (113)

2

8

153

Per cent of drugs

11

2

81 (74)

1

5

100

Figures from Rylander 1966.

The number of Phenmetrazine abusers are given in brackets.

Drug pattern

Stimulant drugs were abused in 81 per cent of the cases. Phenmetrazine was the dominant drug among the stimulants, being used in 91 per cent of these cases, or in 74 per cent of all drug abusers (table 15).

Opiates were abused in 11 per cent, cannabis in 2 per cent, LSD in 1 per cent (2 cases), and other drugs (mainly hypnotics and tranquillizers) in 5 per cent.

When comparing the drug pattern found with that seen in other groups, it is most like the 20-29 year age group of the police cases, both groups having a high record of criminality and a high proportion of abuse of stimulant drugs.

Route of administration

All but one of the 75 cases injected the drugs, whether only stimulants, or other drugs such as opiates or hypnotics. Most of the patients did not use pharmaceutically prepared solutions for injection, but made up their own solution from tablets intended for oral use.

Dosage and administration

A standard dose for many of the abusers was 30, in some cases up to 60 tablets of 25 mg each. To prepare the solution the tablets were crushed, shaken up in water, usually tap water or whatever was available, kept standing for some time, then filtrated through a piece of cotton, the "sieve ", usually in the syringe, the "pump ", and then injected. The first injection ever experienced is called the "virgin sieve" or the "virgin pump ".

The total number of doses amounted to 4-5 per day, or a total of 120-300 tablets per day.

The effectiveness of the "extraction "procedure varied with the technique used. On the whole, a solution prepared from a "standard" dose of 30 tablets of 25 mg each contained 200-300 mg phenmetrazine, corresponding to an effective dose of 7-10 mg per tablet, as determined chemically from filtrates prepared by drug abusers at the Clinic in the presence of the investigator (Rylander 1966).

Two "filtrates" of 60 tablets each contained 547 and 561 mg, corresponding to 9.1-9.3 mg per tablet.

The "standard" doses injected thus contained 200-300 mg (30 tablets) or 400-600 mg (60 tablets); 4-5 injections per day would correspond to 120-300 tablets or a total amount of 800-1,500 mg phenmetrazine !

This should be compared to a therapeutic daily dose of about 75 mg (3 tablets) orally, the abusers using 10 or 20 times the therapeutic dose !

Symptoms

The acute effect of a single injection (the "kick ") is usually described as an enormous feeling of happiness, often called "firing ". Others say that it is like being lifted up in the air under intensive pleasurable sensations: "I almost lost my breath, so wonderful was the feeling ". Many state that the "kick" can only be obtained on injecting the drug, not when taking it orally.

Most former opium and morphine addicts claim that nothing can be compared to the "Preludin-kick ".
* The opiates induce tranquillity and "freedom from troubles ", but lead to passivity and dreams (" down-kick "). The stimulants, however, make the subject feel "alert" and "active" and his self-respect and self-confidence grow immensely (" up-kick "): "The brain goes in top speed ".-" One is capable of doing anything. Problems are put in the background; if they don't fade away you think you will find new ways to cope with them, to master them ".-"Sometimes you think that you are unconquerable. You are sure to be able to do anything, nothing can happen to you".

Preludin is one of the brand names of phenmetrazine.

TABLE 16

Signs and symptoms seen in phenmetrazine abusers with criminal behaviour

Studied at the Clinic for Forensic Psychiatry in Stockholm (Rylander 1966).

Data based on 75 extensively studied patients.

The thought process is affected and associations come easier. "You get so many new ideas and thoughts and you become so profound ". Or, as one critical patient added "or, at least you think that you are profound ".

Perception is accentuated, e.g. of colours. An interior decorator found "harmonic" colours to be more "harmonic ", and "disharmonic" colours to be more "disharmonic ". Sound is accentuated, and high voices and noise are experienced as irritating. In the so-called "drug joints" (" geggar-kvart "), where Preludin abusers gather to take their injections, everything is quiet and low voices dominate.

Taste sensations are intensified, spiced food is said to be too "irritating ". Distilled spirits usually taste repugnant, and most phenmetrazine abusers have stopped taking strong beverages. Wines, especially sweet dessert wines are, however, tolerated, and are sometimes used to finish a bout, when the abuser cannot go on any longer and has to sleep; this is called "de-firing".

Smell may be affected, perfumes and flowers get a stronger smell, and body odours are felt more strongly than under normal conditions.

Phenmetrazine is said to act as an
aphrodisiacum in many instances, increasing both libido and performance. Many abusers have started their abuse by first taking phenmetrazine on week-ends, alone or with their partner, then continuing on Mondays to keep going, and then within a shorter or longer time being "hooked" and taking phenmetrazine on a continuous basis.

One peculiar effect, which also was noticed with the amphetamines, is a forced involuntary or automatic, often meaningless activity, going on for hours, e.g. sorting things in a handbag, taking an automobile into pieces, or wandering on the streets, one person filing his nails for hours, another polishing details on his car all night, or a housewife taking an injection to clean her house.

An abuser of these drugs has very little recollection of what he has done or of the flight of time. Time sense is changed, a certain period of time usually being experienced as much shorter than in reality.

The ability of stimulant drugs to reduce sensations of fatigue and sleep is very prominent in phenmetrazine abusers. As soon as the effect of an injection is beginning to fade away, usually after 4-5 hours, a new injection is taken. This may go on day after day up to one to two weeks with no real sleep; some abusers doze for an hour or two, others even less than that for several days. Food intake is often reduced, and the abuser may become emaciated. Finally the desired effects can no longer be maintained. The "pump ", i.e. the syringe, "does not fire any longer ". The abuser becomes weak and exhausted, and feels completely "finished ". Some may fall into a deep sleep, a so-called "de-firing ". Others may experience a so-called "mis-firing" with fear, anxiety, restlessness and nightmares. Many take barbiturates or wine to produce a good "de-firing ".

Depending on the intensity of the abuse - doses, mode of administration and frequency - the personality structure and the effects induced by the drug taking, the environment and the availability of the drug (i.e. availability of drug and the money to buy it), the patient may under certain circumstances quit the habit, or take it up again and go on injecting on a more or less continuous basis. The relapse rate in the cases studied has been very high.

Abstinence symptoms

It was earlier claimed that withdrawal in cases with chronic abuse of stimulant drugs would not lead to an abstinence syndrome. Rylander, however, considers the symptoms appearing in many chronic abusers after withdrawal of injections of phenmetrazine as part of a typical abstinence syndrome. The symptoms are dominated by anxiety and fear, restlessness, spasms, sweating, heat flushes and dryness in the mouth. A forced, intensive craving to obtain phenmetrazine at any price is experienced in severe cases. "You are driven by your fear and anxiety, hour after hour, to procure more Preludin ", is a typical description.

These reactions are effectively and rapidly blocked by hypnotics, many psychopharmacological agents and by food. Detoxication is no problem under medical supervision and control.

A strong psychic dependence on stimulant drugs, probably stronger for phenmetrazine than for other stimulant drugs, exists and lasts in many instances for a long time after the patient is off the drug.

Tolerance phenomena exist; the dose has to be increased to produce the same effect, and finally even after large doses the effect is definitely reduced (" defiring ").

If the patient has been off drugs for some time, and had enough sleep, food and rest, a new and often lower dose may again produce the desired effect - the "kick ", "ignition" or "firing ", and even be experienced as the "virgin sieve ".

Toxic psychoses

Toxic psychoses are seen in many chronic phenmetrazine abusers. These psychoses may be very severe with anxiety, fear and paranoid delusions being more dominating and more frequent than has been described for amphetamine psychoses. Paranoid delusions are so common that the abusers themselves speak of" noia" (from paranoia). "Every one of us gets noia ", was the statement of an experienced abuser. Sixty-five per cent of the patients studied have had paranoid psychosis.

A toxic psychosis with a strong paranoid reaction can come after a short period of abuse, in one patient after three weeks of intensive phenmetrazine abuse. The patient ran from house to house to escape his "pursuers ", and was almost run down by a car, when rushing in panic over a street filled with heavy traffic to hide himself under a bush in a park.

The paranoia may be centered around the police ("police-noia"), or in other cases be directed against members of the same group, friends or others.

Illusions are common. Parking meters become policemen, flowerpots are turned into faces, traffic signs are men, branches on trees along the road are arms catching the individual. Acoustic and visual hallucinations exist.

A certain insight into the disease, into the pathological nature of the illusions and hallucinations may exist in an early stage. The patient "knows" that his experiences are caused by his phenmetrazine intake, that persons passing are not pursuers etc., but he is still anxious, fearful and even panic-stricken.

In advanced cases the patient loses contact with reality, and is dominated by panic with confusion; paranoid ideas and illusions mark his behaviour. One patient jumped out of the window, but fell on a sunblind, landed on the street unhurt, and escaped. Another took a car and drove at menacing speed through rush-hour traffic until he hit another car. A third drew his knife when asked by a policeman why he was parked at a "No Parking" sign. A fourth tried to jump from a balcony on the ninth floor for fear of menacing voices, but was stopped by somebody catching him by the foot when he was already over the balcony.

Criminological aspects

Because the patients studied were examined for violations of the law they were also asked about the possible influence of phenmetrazine on their criminal behaviour. Two-thirds stated that phenmetrazine intake made them bolder and more daring, inducing them to take more risks; about the same proportion stated that after phenmetrazine they did more criminal acts, often out of boldness, not for obtaining the money.

Many criminals have switched from alcohol to stimulants. It has been observed e.g. that safe breakers, who earlier took large amounts of alcohol while waiting for the right moment to break the safe - the alcohol often making them so intoxicated that they failed - now take injections of phenmetrazine.

A summary of the symptoms seen in 75 extensively studied patients, is given in table 16.

Rylander summarizes the results of his findings and those of others with the statement that in many respects phenmetrazine taken intravenously is more dangerous than morphine and opium, which only rarely lead to psychoses and do not possess such rapidly devastating psychical and physical effects. It was thought earlier that phenmetrazine had considerably weaker effects than the amphetamines; the light depressions and the psychopathic conditions that arose out of phenmetrazine abuse were said to be easily treated and it was denied in many quarters that tolerance, dependence and abstinence symptoms could emerge. Already, when phenmetrazine was used as a weightreducing agent it became clear, however, that dependence could arise and that toxic psychoses could emerge during prolonged abuse.

From Rylander's material it must be concluded that the present epidemic spread, the prolonged intake of high doses for many weeks and the psychotoxic effects, which often seem to be more frequent and more severe in individuals with a peculiar personal make-up (such as sociopaths, schizoid personalities, criminals and others), are important elements in the picture of phenmetrazine abuse.

SOMATIC COMPLICATIONS: SEPSIS, INFECTIOUS HEPATITIS

With a great number of individuals abusing narcotic drugs and injecting them under non-hygienic conditions, not observing sterility, using ordinary water for preparing the solution for injection from crushed tablets, and often employing the same syringe and cannula within a whole group of abusers - it would only be logical to assume that these habits would result in a number of somatic complications. Arising out of the transfer of bacteria and viruses, the complications actually range from local thromboses and infections, scars and tissue induration, to sepsis and infectious hepatitis.

Sepsis

Seven severe cases of sepsis in drug abusers have been treated in the last few years in Roslagstull Hospital (Ekman and Ström 1967). The first two cases, two brothers, were admitted as far back as August 1962, and one of them died. The other five, all women, were seen in 1964-1965, and all are surviving. They had injected large doses of stimulants, and also other drugs, for considerable periods of times. Hemolytical
streptococci were found in one case, and
staphyloccus aureus in four. All cases had been severely ill and showed complications of various kinds during and after the hospital stay, among others, endo- and myocarditis and pleuritis.

Infectious hepatitis

The cases of infectious hepatitis - also named epidemic inoculation, viral or serum hepatitis - occurring in the Stockholm area are treated mainly in one hospital, the Roslagstull Hospital. The first cases were seen in November 1962. Since then the
number of cases has increased rapidly, from 2 in 1962, to 14 in 1963, to 81 in 1964, and to 269 in 1966; in 1967 there were 275 cases in the first seven months, thus a logarithmic or exponential increase, being one expression of a transfer mechanism from one individual to another. In 4 years a total of 712 cases were observed. The men dominate, being 75 per cent of the total (Ekman and Ström 1967. Detailed figures are given in table 17).

This increase seems to reflect quite well the epidemiology of the drug abuse picture in Stockholm during these four years. In addition it must be stressed that every single case of diagnostisized manifest infectious hepatitis with jaundice must represent a fairly great number of drug abusers, because only a minority of those infected will get the disease in a manifest form (Ekman and Ström 1967).

The
age distribution in these cases is typical. The dominating age group among the men was 20-24 years (40 per cent of the total), with no less than 25 per cent being under 20 years of age. Only 6 per cent were over 40 years. The mean age was 25.8 years.

In women the dominating age group was 15-19 years (49 cases), representing 43 per cent of the total. In addition two girls were under 14 years. Another 36 per cent were 20-24 years; only one case was over forty. The mean age was 22.2 years.

An analysis of the first 100 consecutive cases (75 men, 25 women) treated in the period 1962-1964, all having injected narcotic drugs within six months before the appearance of their hepatitis, were described by Agell, Lundbergh and Svenbom (1965).

The age of the patients varied between 17 and 43 years, the average being 24 years. Mainly stimulant drugs had been abused, being taken by injection with phenmetrazine and methylphenidate dominating the picture which were combined in a number of cases with morphine; in some cases the stimulants were taken with morphine alone. Forty-five patients had injected the drugs at least once a week, of these 23 almost daily. In 55 patients the abuse had lasted up to one year.

In 40 per cent the hepatitis started more or less suddenly, in the rest of the cases more slowly.

Bilirubin, thymol, alcaline phosphatase, GOT and GPT were checked once per week. The results coincided with those in infectious (serum-) hepatitis of other origin.

Liver biopsies carried out in 66 cases showed microscopical changes typical for progressive or regressive hepatitis; in 23 per cent various stages of tissue increase were seen.

The behaviour of these young patients necessitated that the treatment in hospital be discontinued only after two weeks in 53 per cent of the patients, after which they were put on an out-patient basis.

TABLE 17

Infectious hepatitis in drug abusers in Stockholm 1962-1966

Men

Women

Age

n

Per cent

n

Per cent

10-14

2

1.7

15-19

81

25.0

49

43.0

20-24

127

39.4

41

36.0

25-29

51

15.8

14

12.3

30-34

25

7.7

4

3.5

35-39

20

6.2

3

2.6

40-44

8

2.5

1

0.9

45-49

4

1.2

50-

7

2.2

Total

323

100.0

114

100.0

Mean age

25.8

22.2

Adapted from Ekman and Ström (
Läk. tidn. 1967,
64:4083).

In 48 per cent the drug abuse continued after the hospital period, and in 22 per cent it lasted during the hospital stay ! An after-control in 27 of these patients showed permanent disturbed liver function in 16, or in 60 per cent of those continuing the abuse (Agell
et al. 1965).

A recent survey by Ekman and Ström (1967) discusses an analysis of a further 100 cases (77 men, 23 women); 91 had abused phenmetrazine (Preludin), in 24 cases combined with methylphenidate (Ritalina), and in 11 also with other drugs; 9 had abused morphine, all cases by injection.

Bilirubin was relatively low in these cases, transaminases (GPT and GOT) were elevated, the thymol test was regularly increased, and as a rule not normalized within an observation period of 6 weeks. Alcaline phosphatase, and in a number of cases also cholesterol were elevated; bromsulphalein and galactose tests showed pathological values in about one third of the cases. The course was essentially the same as that seen in epidemic hepatitis of other origin.

The hypothesis was brought forward that the stimulant drugs abused may not show a liver-toxic effect
per se in persons with normal livers, but are more or less toxic when taken by an individual who has, or has had, a hepatitis.

During the treatment of hepatitis in the hospital sudden rises of bilirubin were seen, most likely due to injections of narcotic drugs
during the hospital stay. Likewise the same phenomena were seen after a hospital stay in the course of recurrent periods of icterus. In a typical case a patient injecting the stimulants again, showed a sudden rise in the transaminases followed by a new clinical deterioration with pathological elevation of all liver tests and a new icterus. In these cases, therefore, the prognosis over a longer period of time seems to be doubtful (Ekman and Ström 1967).

A study of 103 cases (91 males, 12 females) of infectious inoculation hepatitis in criminals (Bellander 1965), appearing during one year, 1963-1964, among arrested or prison inmates, showed the same general picture. The majority of the patients were between 20 and 30 years. The majority of the drugs abused were stimulants, phenmetrazine and methylphenidate, in some cases also opiates (mainly dextromoramide), and in some cases barbiturates, mainly mebumal. Besides the increase in bilirubin and in enzyme titres (transaminases) complications in the form of arthritis were common.

Ten patients, all being intravenous drug abusers (9 males and 1 female) were also treated for infectious hepatitis in Danderyd Hospital. Their average age was around 25 years. They had all acquired their hepatitis after abusing stimulant drugs by injection. Severe behav- ioural disturbances were noted in some cases (Stenberg 1965).

The disciplinary problems were discussed by Ström (1965) who pointed to the great difficulty in keeping these young patients together with others in the hospital ward without risking an "epidemic" spread of their drug abuse to the other patients in the ward.

It should also be noted that among the 169 juveniles, studied by Herulf and Sunesson (1967) in the Children's Welfare Board in Stockholm no less than 50 per cent had had infectious hepatitis; 16 per cent had been referred to the Board from the Roslagstull Hospital.

Finally it must be stressed that the transfer of infectious hepatitis occurs not only from individual to individual, using the same syringe within a narcotics drug sub-group, e.g. within a "drug joint" (" geggar-kvart "), i.e. a place where drug abusers stay together and take their drugs, but also from the abuser to other persons outside the abuse group, e.g. to hospital or laboratory personnel handling blood samples from narcotic abusers, and to patients, transfused with blood originating from a drug abuser with latent virus hepatitis. These consequences are only now being realized, and will necessitate a series of protective measures; these are under discussion in Sweden.

One part in the study of drug abuse is the problem of identifying the drugs taken by the individual, determining the concentration of the drug in the body and evaluating what the level found means under various circumstances.

The methods used to identify drugs can principally be divided into (i) screening methods to determine the presence or absence of various groups of drugs and if possible identify the actual drug(s) taken, and (ii) quantitative methods to determine the actual concentration of the drug(s) identified.

Screening methods: These methods should be relatively easy to apply, and as far as possible should tell not only about the presence of
groups of drugs, but also, if possible, identify the
actual drugs present. Even if several drugs are taken simultaneously, a good screening method should be able to identify them, in spite of possible interference during the analytical procedure. The groups of interest range from opiates (both natural and synthetic), stimulants (at least three different types, amphetamine, phenmetrazine and methylphenidate), hypnotics (both barbiturate derivatives and non-barbituric substances, e.g. glutetimide), and also the whole line of sedatives, tranquillizers and other psycho-pharmacological agents, e.g. meprobamate, diazepines, phentiazines a.o., and if possible marihuana and hallucinogens, e.g. LSD.

Quantitative methods: These are naturally of another order of difficulty, because they must have a high precision and accuracy to give reliable quantitative data. They must also be specific to be able to identify the drug and differentiate between the drug, its metabolites and parent compounds with similar effects. Finally, they must have a high degree of sensitivity to be able to detect the minute concentrations that appear of a drug in blood or urine, especially when so many of these drugs are given in µg-doses (meaning thousandths of 1 mg) in the blood or urine.

Quantitative methods are based on a number of various procedures, ranging from classical chemical methods to enzymalic procedures, spectrophotometry, fluorescence- photometry and infra-red techniques, to gas chromatography and mass-spectroscopy.

And lastly, when a number of samples have to be analysed within a short time span, automated procedures must be contemplated in order to cope with the results.

A number of methods do exist, but there are still, and always will be, gaps to fill.

Many existing methods so far work well on large urine samples, around 50-100 ml, but have to be improved to be used on blood, and especially if to be used in the micro-range, on blood samples below 1 ml.

New chemical methods have to be worked out, or existing methods have to be improved, to detect the presence of cannabis, or some of its break-down products in the urine. The same is true about LSD for which so far mainly biological approaches have been tested on a larger scale; this also applies to the amphetamines, where better methods, mainly using blood, are needed.

Speaking generally, many of these methods have to be modified to be applied for routine use, e.g. on an automated basis.

It must be added that very few cross-national and international studies have been carried out to evaluate and improve existing methods, which often differ from laboratory to laboratory, even within the same country. Such studies are necessary to determine precision and accuracy, sensitivity and specificity, and standard reference samples need to be sent out to standardize analytical procedures, and get comparable results everywhere.

Another important part of this research is to study the actual metabolism of a drug, i.e. its fate in the body - blood levels reached, metabolites, site(s) and mechanisms of breakdown and disappearance (by conjugation, breakdown, excretion, etc.), and the timecourse of blood and urine levels.

The possible interference of the drug with other enzyme systems, and with the metabolism of other drugs, the breakdown rate of which might be accelerated or depressed, is also an important problem.

Further, the correlation between dosage and resulting blood and urine levels, and the time-course, will have to be elucidated in order to tell what a certain concentration may mean in terms of effect.

Finally, the metabolism must be studied in different persons, and not only of therapeutic doses (because large variations of 20-30 times in metabolic rate have been observed), but also, if possible, of excessive doses, to see if these large doses are handled differently in the tolerant organism, by change in metabolic-enzymatic mechanisms or in CNS-localized synaptic transmittor-enzyme-systems, or by other mechanisms of integration and transfer of effects in the CNS.

Knowing the time-course, of the drug and its metabolites in blood and urine will help to evaluate the magnitude and time effect of a dose taken, e.g. in a case of intoxication.

Only a limited number of drugs have so far been studied in the elaborate way sketched. The work involved is enormous, and necessitates international co-operation.

Quantitative methods and studies on metabolism are necessary for a proper evaluation of the effects of a drug on various functions. The ideal would be to study the effects quantitatively by a battery of tests, to correlate the effects found to the existing blood level, and to study the variations in blood level, metabolism and excretion after various doses.

Further possible mechanisms of reaction to prolonged intake have to be studied: adaptation, if possible tolerance, dependence and withdrawal (and their metabolic, physiological, behavioural and psychological correlates) as well as the problem of assessing in quantitative terms the difference in the effect of a therapeutic dose and the excessive amounts - 50-100 times the therapeutic dose - which are taken by abusers.

To study the points stressed in detail is a challenging task that only can be done by engaging a number of laboratories, each taking one part of the problem, and there must be a close co-operation to share experience and methods and to avoid duplication.

A number of direct applications of the problems posed can be pointed to.

Screening methods and quantitative procedures have several important uses:

The clinical chemistry laboratory, which is given the problem of diagnozing a case of acute intoxication, employs these procedures to identify the drug and to tell the concentration as one important basis for instituting the proper therapy, e.g. the administration of the proper antidote etc., and to follow changes in the concentration as a guide for the therapeutic management.

The procedures have medico-legal applications, e.g. to (
a) analyse a case of "drunken driving ", and differentiate between alcohol and drugs, and identify the drug, or (
b) in a case of severe alcohol intoxication to eliminate the possibility of a mixed intoxication of alcohol + drugs with its highly increased risk of complications.

The procedures are used for diagnostic purposes in cases of drug dependence to make the diagnosis as to what drugs are really abused, their identity and their concentration in the blood as guides to assessing the doses taken.

In diagnostic work, they are also used to check a drug abuser during a treatment programme by controlling a urine sample to ensure (
a) that the patient really has stopped taking the abused drug, and (
b) that he is not taking other drugs.

Such a procedure is felt by many well-motivated patients to help in his trying to stick to a treatment programme, knowing that any drug-taking will show up in the urine control. The psychological mechanism is not unlike the one in using a "protective" drug-disulfuram or CCC (temposil) as an adjunct in the treatment of alcoholism.

Studies along all the lines surveyed are proceeding in several laboratories in Sweden. The aim is to improve methods of detection and analysis, make studies of metabolism, of the action and the correlation between dose, blood levels and effects, and there are pilot studies of drug abusers to follow the effects of excessive doses, and also studies in treatment procedures taking regular urine checks of patients.

A survey of the material so far collected is under way; some preliminary results were reported by the Narcotics Drug Committee (1967:25). A more close and active co-operation between different laboratories is in the planning stage and will go into effect within a short time. Manuals on existing methods are being planned, as well as attempts to standardize procedures on a national basis, and assign certain types of analyses to interested laboratories, having the necessary equipment, personnel and capacity. Even a wider co-opera- tion involving several interested countries is envisaged, with such help as may be obtained from the Laboratory of the United Nations Division of Narcotic Drugs, and the World Health Organization, both in Geneva.

Drug dependence and drug abuse can be looked upon as two phases of the same problem, one term stressing more the medical and biological angles, the other the medical and social angles, both also involving psychological and legal aspects. The treatment of individuals with drug dependence or drug abuse must thus be founded on a complex multidimensional approach, stressing the impact of somatic, psychiatric, psychological and social factors on the origin, development and course of the disease. This means that social care will play an important role in rehabilitation together with specific medical measures.

In the deliberations of the Swedish Narcotics Drug Committee, the evaluation of treatment facilities plays an important part, and is given at length in its Report I (1967:25); in the present survey only the more general principles of the therapeutic approach can be discussed.

The aim of a treatment programme will depend on the factors involved in the origin and course of the disease and on the state of the patient at the time of treatment. When acute intoxication is present the immediate aim is to treat the intoxication and make the patient survive, the intake of an overdose not being an uncommon fate. Several deaths have occurred, not only due to an overdose given by an old abuser to a non-drug dependent person, but also in the case of individual drug users due to overdoses and mixtures of different types of drugs.

When the patient is in a chronic state the ultimate aim must be to make the patient stop the intake, i.e. a detoxification, followed by treatment of the withdrawal symptoms and rehabilitation in a drug-free environment to give the user a place in society again and prevent his relapse into drug use. In some cases the immediate aim will be to make him function socially, the withdrawal being secondary to this goal.

Special problems will be posed by drug abusers who have shown a great number of relapses, and who have little or no chance of being in a drug-free life or of finding a degree of social rehabilitation. In these cases it may be argued that the aim must be limited to reducing the personal misery, preventing the contagiousness of the abuse, and preventing as far as possible criminal and other anti-social behaviour.

One great difference between many patients with drug dependence or drug abuse and patients with other diseases, e.g. somatic diseases, is the difference in motivation to seek treatment. Patients with drug dependence due to iatrogenic reasons, e.g. induced through prolonged medication for a somatic disease, or who have become dependent following accidental intake in a group with which the patient does not agree, are strongly motivated. On the other hand those drug abusers, who have" chosen" their type of drug intake, - whether as a symptom of an underlying, usually psychic, disturbance, or as a result of choosing a special environment, a group or a "sub-culture " - usually have very little insight into their disturbance, and are not motivated to seek treatment.

Some drug abusers will need medical "intensive" treatment - detoxification, or other medical care, e.g. for inoculation hepatitis, whereas the majority will need psychiatric treatment of one or the other kind, combined with other measures. In any case an integration of all available forms of treatment is necessary, and must be achieved in the planning stage, in order to avoid the transfer of a patient from one treatment centre to the other (" the revolving door "). The strong connexion with one therapeutic unit or team - from the initial contact over the intensive period to the aftercare - is an integral part of a successful treatment programme.

Treatment in hospitals

The treatment of drug abuse must necessarily be extended over a long period of time, during which the stay in a hospital will be only one part.

Somatic wards: Somatic complications must be dealt with as required by the severity of the condition. The treatment may range from treating acutely intoxicated patients by intensive care of an anaesthesiological nature, including administration of oxygen, artificial respiration, prophylaxis of secondary shock and infection etc., to treating infectious hepatitis, sepsis, etc., in epidemic hospitals.

Often young drug abusers have been so aggressive, have smuggled drugs into the ward and even contaminated other patients with drug abuse that treatment of several patients at the same time in a medical ward, e.g. for hepatitis, has proven difficult; many of these patients had to be treated on an out-patient basis (Ekman and Ström 1967).

Psychiatric hospitals: Several different principles of treatment are being tried at present. One is to treat drug abusers together with other patients in the ward, another is to form special wards with 10-12 beds, under specially trained personnel so that withdrawal and rehabilitation are carried out in the best possible conditions.

Both principles are being tried, in Sweden the choice depending among other factors on the type of patient, and the type of dependence. Generally it is assumed that during the initial period of treatment rather strong rules have to be kept, the patient not being allowed to leave the ward until a considerable time - several weeks - has passed, to ensure that his rehabilitation and "indoctrination" period is properly started in order to minimize the risk of relapse.

In all these cases urine samples must be analyzed at regular intervals to check that the patient has stopped taking the drugs abused and is not taking other drugs than those prescribed.

Such a urine analysis implies a technically highly developed laboratory. This requirement can be filled by sending samples to a regional laboratory, if the hospital itself lacks the facilities.

Out-patient treatment

As a rule an out-patient treatment with any chance of success is only possible with few patients of special types and under special circumstances, e.g. those in the preliminary stage of a treatment and in the after-care stage, because total abstinence from drugs and a drugfree environment are two necessary factors in outpatient treatment.

Maintenance

The question of "treating" drug-dependent patients by maintaining them on drugs has been the object of discussion for a very long time.

In a few selected cases, mainly opiate-dependent patients, who have been in hospital for treatment a great number of times for many years, who have relapsed many times, and who are well-adjusted in society, a maintenance therapy has been tried after conferring with the Swedish National Medical Board. In these cases the patient was treated by one doctor only, and obtained his drugs from one pharmacy only.

Now, following the experiment by Dole and Nyswander of New York, a limited number of opiatedependent patients, while in the hospital on a strict regime, are being transferred from their own intravenous administration of opiates to oral intake of methadone in fruit juice, given each morning in the hospital. After some weeks in the hospital the maintenance schedule is followed on an out-patient basis. The urine is checked daily, or twice a week, for presence or absence of other narcotic or CNS-active drugs. The ultimate goal, apart from a medical and social rehabilitation, is to make these patients abstinent with regard to opiates.

As for abusers of stimulant drugs the conditions seem to be completely different. One large-scale experiment was started in 1965, a number of private doctors being allowed to maintain abusers of stimulant and/or opiate drugs on prescribed drugs. The majority of the doctors discontinued the scheme, because most of the patients became unmanageable.

Some doctors, however, continued in spite of the situation getting out of control. The patients came at all times of the day, demanding increasing doses of various drugs, the prescriptions were filled by the doctor without proper control, and many patients managed, besides using the drugs themselves in large doses, to induce others to start taking drugs or maintained other abusers on drugs, (" satellite" cases), or they sold part of the drugs obtained. Several accidents have also happened, there have been suicidal attempts, overdoses in satellite cases, and one death due to an overdose given to a satellite.

The whole group of these drug dependents on stimulants - mainly phenmetrazine - has now been transferred to a specially equipped out-patient clinic for ultimate detoxification, rehabilitation and referral to other institutions. During the period of reduction of doses, urine samples for drug control are analyzed regularly. A scientific study of the background, drug history, criminal background, social adjustment and development is in progress (Bergsman and Järpe); a final evaluation of the outcome will have to await the completion of this survey.

Young drug abusers: The problems are partly different with regard to young drug abusers. In most cases the drug abuse in juveniles is a symptom of an underlying disturbance of a psychic or social nature. The treatment must be directed to the underlying cause, and thus in many cases be of a different type than in adults; in the juveniles the environmental factors can often still be discerned separately from those connected, for example, with changes in personality structure, or other traits. Thus these young cases are as a rule very similar to other pediatric-psychiatric patients.

An intimate co-operation and integration between the medical and the social sectors is necessary; the rehabilitation, after-care and follow-up are extremely important, and often necessitate other means, such as placing in foster homes, treatment homes, youth homes, or youth treatment schools.

The demand on the psychiatric clinics has so far not been too great, but the demand on the other institutions is greater. Out of the 243 juveniles in youth homes in Stockholm on a certain date (14 January 1967) 83, or 34 per cent, were drug abusers; in 46 cases drug abuse was the main reason for referral.

No definite rules can yet be given as to principles of treatment. The problem is urgent, as the number of juvenile drug abusers is rapidly increasing. Treatment is still experimental and is following several lines; a proper evaluation of various forms of treatment is yet to be made.

Search groups

Due to the lack of motivation by many drug abusers to seek treatment and to the special composition of many of the "drug-joints" where abuse prevails, it is necessary to organize some type of "search" group. This group looks for the drug abusers in the places where they are found, - in slum areas, in the "drug-joints" (" geggarkvart "), in certain parks etc., tries to help them with their immediate problems (housing, food, or clothing), and tries to motivate them to seek treatment. Other tasks are to find, and if possible to isolate the "contaminating" person, to break up "joints" in co-operation with other agencies, and to help those who are parts of the "joint" to adjust to new ways of life.

Such "search groups ", composed of social workers and voluntary personnel, must have access to a sociallyoriented psychiatrist at all times of the day. The members of the search group must stay together for long periods of time to obtain an intimate knowledge of the conditions, places and persons involved, and to be able to help parents to trace and get children that may stay with a "drug-joint" and persuade them to go back home under circumstances when, according to existing legislation, the help of the police cannot be obtained.

Other treatment centres and organizations: Voluntary organizations have proven to be effective in selected cases, e.g. rehabilitation centres attached to the church. The patient after an initial detoxification in the hospital is transfered to the centre. He leaves his old environment, and comes into a new milieu and gets new interests in life; very successful results have been obtained in a number of selected cases.

Half-way houses, day- or night-clinics are also of importance as stations on the way to get the patient back to normal life. Close co-operation with organizations and institutions working with treatment, care and after-care of alcoholics is considered useful.

A National Committee for Help to Drug-Dependents (RFHL), based on voluntary membership, was organized in March 1965. RFHL has had contact with a total of some 400-600 patients, and has helped them to adjust in society. It has contacted various organizations and hospitals, motivated many persons to seek treatment, who on their own would not have contacted medical institutions, and has tried to keep informed on the development of these cases.

Some data concerning the activities of RFHL have been surveyed by the Narcotics Drug Committee (1967:25).

During 3 months in 1966 a total of 40 patients were seen, 31 (77 per cent) of these abused stimulant drugs and 9 opiates (23 per cent). Half of them had abused alcohol. Only 6, or 15 per cent, held a job, the others, had no job, or were receiving medical insurance payments. One-fourth (27 per cent) had no home, and slept in slum-houses, etc., changing them every night.

In 60 per cent of cases these persons had had contact with the police, 45 per cent had been in prison.

Among medical complications it can be noted that 50 per cent had been treated in mental hospitals, and 58 per cent had had infectious hepatitis with jaundice.

During the latter part of 1966 the emphasis was put on helping younger persons. In the four-month period August-November 1966 a total of 212 persons were seen; the mean age was 21 years.

RFHL tries to work through a social worker, a group therapist and voluntary personnel, to help to make the drug users willing to accept treatment - a total of 85 being referred to physicians - to contact social agencies, and to stay out of the old gangs. RFHL is also helping parents in understanding their children, and children in accepting help from outside.

The setting up of groups of former patients on the lines of Alcoholics Anonymous is in the planning stage.

As a background to the understanding of the drug problem the consumption of medicaments in Sweden is given here, the figures being obtained from a Report on Medicaments (SOU 1966:28) by courtesy of the Society of Pharmacists.

In the period 1922-1966 the turnover of medicaments has increased 20-fold, from 38 million Swedish crowns (about 7.3 million US dollars) in 1922 to 773 millions (about 150 million dollars) in 1966.

The number of prescriptions per year, known for the period 1939-1966, has risen by a factor of 4, from 8.4 to 33.8 millions.

The mean cost per prescription known for the period 1955-1966, has increased two-fold, from 6.49 to 14.60 Sw.cr. per remedy. (See table 18.)

When evaluating the rate of increase, the general turnover of medicaments is increasing by 10 per cent per year, the average cost per prescription by 7 per cent per year, and the number of prescriptions by 3 per cent per year.

For comparison it can be mentioned that the total population is increasing by less than 1 per cent per year.

The types of drugs being abused comprise analgesic drugs, including opiates and non-narcotic analgesics, representing about 9 per cent of the total consumption of remedies in Sweden, hypnotics, sedatives and tranquillizers about 13 per cent, and stimulant drugs only about 1-2 per cent of the total legal consumption.

TABLE 18

Turnover of medicaments, 1922-1966

Year

Turnover in millions Sw. crowns

Number of prescription

Average cost per prescription Sw. crowns

1922

38.2

-

-

1927

37.2

-

-

1932

39.4

-

-

1937

50.7

-

-

1939

58.5

8.4

-

1944

92.5

13.7

-

1949

140.0

17.6

-

1952

195.0

19.7

-

1953

204.7

20.4

-

1954

216.5

20.9

-

1955

242.9

20.4

6.49

1956

279.6

21.4

7.21

1957

322.6

23.4

7.83

1958

354.1

23.8

8.52

1959

376.2

24.5

8.91

1960

412.7

26.3

9.45

1961

454.0

27.3

10.20

1962

501.6

28.5

10.82

1963

553.2

29.7

11.56

1964

613.3

31.2

12.36

1965

702.6

33.5

13.40

1966

773.0

33.8

14.60

Figures obtained from the Swedish Society of Pharmacists.

Opiates

The development in the consumption of opiates for the period 1959-1966 has been surveyed by the Narcotics Drug Committee (1967:25 and 1967:41).

During the 7-year period 1959-1966 the total consumption of opiates, whether of natural or synthetic origin, has decreased by 65 per cent, from a total of 18.7 million doses in 1959 to 6.6 million doses in 1966 (table 19, figs. 16 and 17).

When considering the various drugs, the consumption of morphine has decreased most in these 8 years from 4.5 million doses in 1959 to 1.5 million doses in 1966, or by 67 per cent, whereas the synthetic drugs have decreased somewhat less from 6.5 million doses to 3.0 million doses or by 54 per cent on an average (table 19).

The only drug increasing in use has been pethidine by 64 per cent, due to the trend of substitution of synthetic drugs for morphine; the increase does not, however, in any way compensate for over-all reduction, the increase being from 0.5 million doses in 1959 to 1.4 million in 1966.

TABLE 19

Consumption of some analgesic narcotics (in millions of doses)

Year

Morphine (l0 mg)

Oxicodone (10 mg)

Hydrocodone (5 mg)

Pethidine (50 mg)

Ketobemidone (5 mg)

Methadone (5 mg)

Dextromoramide (5 mg)

Total

1959

4.5

2.4

5.3

0.5

1.8

2

2.2

18.7

1960

3.5

2.3

6.7

0.4

1.8

2

0.7

17.4

1961

3.1

2.4

5

0.5

1.6

1.3

0.5

14.4

1962

3

1.5

3.7

0.8

1.2

1.3

0.4

11.9

1963

2.1

0.9

1.5

0.5

1.2

0.2

0.3

6.7

1964

2

0.8

1.6

0.9

1.1

0.2

0.2

6.8

1965

1.8

0.8

1

0.8

1.1

0.4

0.2

6.1

1966

1.5

1.5

0.6

1.4

1.0

0.4

0.2

6.6

Figures from Narcotics Drug Committee Reports I and II (1967:25,41).

Two stages are seen in the curve representing the rate of decrease, one between 1960 and 1961, and one between 1962 and 1963. In November 1960 the National Medical Board sent out a warning to all doctors about the abuse of analgesic and stimulant drugs, naming which drugs had been mostly abused, and telling some of the ways in which abusers procured the drugs.

In November 1962 the National Medical Board sent out a new warning for drug abuse, and reduced the right to prescribe drugs by telephone. These two measures are clearly seen in the sales figures. The consumption of opiates has become stabilized on a constant level for the last four years (figs. 16 and 17).

Stimulant drugs

The figures have been surveyed by the Narcotics Drug Committee (1967:25 and 1967:41).

Fig. 16. Consumption of narcotic drugs in Sweden 1959-1966 (yearly turnover). Figures obtained from the National Medical Board. 1959: Stimulant drugs (amphetamines already in 1944) put on the National Narcotics List, e.g. phenmetrazine and methylphenidate. 1960: Warning about the risks of abuse of narcotics, including stimulants, issued to the medical profession by the National Medical Board. 1962: Limitation in prescription rights of narcotic drugs, especially of prescription by telephone. Narcotics prescriptions: Number of prescriptions of narcotic drugs.

The reduction in the sale of stimulant drugs in the period 1959-1966 is dramatic, from a total of 33.2 million doses in 1959 to 7.2 million in 1966, or by 78 per cent. Some differences between the various drugs are noticed in this trend.

The amphetamines (amphetamine + methamphetamine) increased up to 9.5 million doses in 1960, then fell to a minimum of 1.6 million doses in 1964, and have now increased again to 5.9 million doses. Dexamphetamine decreased from 22.0 million doses to 0.5 million in 1966, or by 97 per cent (table 20, fig. 18).

The sale of methylphenidate dropped by 63 per cent, from 2.2 to 0.8 million doses.

The legal sale of phenmetrazine dropped from initially 8.4 million doses a year to zero, phenmetrazine being prohibited from December 1965.

Thus the legal sale during the last few years of those stimulant drugs that were mostly abused, viz. phenmetrazine and methylphenidate, was only a fraction, about one million tablets a year, of the amount that must have been furnished by the illicit market. The illegal consumption, when judged from the large number of drug abusers and the immense doses taken by these abusers (up to 100-300 tablets a day !) must be estimated to be around 20-40 million tablets a year, or even more, thus 50,000-100,000 tablets per day.

Prescriptions: A similar picture is shown by the change during the period 1959-1966, in the number of prescriptions for "narcotic" drugs-which in Sweden comprise opiates, cannabis, coca leaves and cocaine, centrally acting stimulant drugs and hallucinogens (fig. 16).

During this eight-year period the number of prescriptions dropped by 83 per cent, from 762,913 in 1959 to 127,950 in 1966.

SALE OF SYRINGES AND CANNULAS

Syringes and cannulas are used for medical purposes in hospitals which procure them directly from wholesale dealers. They are also used by out-patients for self-administration of certain remedies, mainly by diabetics for insulin, and by asthmatic patients for bronchodilating agents. These out-patients usually obtain the syringes and cannulas needed on a doctor's prescription from pharmacies or certain shops specializing in surgical instruments and equipment of that type; syringes and cannulas can also be bought directly without a prescription.

On the whole, the sale to out-patients has been rather constant. A tendency to substitution of glass syringes and cannulas by disposable syringes, made of plastic material and intended for single use only, has been noted in later years.

During the last few years, however, it has been noted both by pharmacies and shops selling surgical instruments that an increasing number of individuals are buying syringes and cannulas. These individuals are often dishevelled, boisterous, badly-clothed, shaky or "high ", with an increasing proportion of school-children among them, especially in centrally-located pharmacies in the larger cities.

Two studies were therefore made by the Narcotics Drug Committee.

In the
first study, carried out 15 November - 15 December 1965, all pharmacies in Sweden and the two largest surgical-instrument firms were asked to note the number of syringes and cannulas sold to single customers.

A total of 14,400 cannulas, 500 glass syringes and 3,600 disposable plastic syringes were sold during that month.

Daily fluctuations existed. A decrease was noted in the middle of the observed period during a series of four TV-programmes on narcotic drugs, and an increase after the end of that series.

A
new study was made one year later during a period of 2 weeks, 7-21 October 1966. Again all sales were noted both in pharmacies and surgical instrument shops, but the sex and approximate age of the buyer was also taken down.

TABLE 20

Consumption of some stimulant drugs (in millions of doses)

Year

Amphetamine + methamphetamine (5 mg)

Dexamphetamine (2.5 mg)

Phenmetrazine (Preludin) (25 mg)

Methylphenidate (Ritalina) (10 mg)

Total

1959

2.8

22

8.4

-

33.2

1960

9.5

9.5

7.9

-

26.9

1961

4.2

9

3.5

2.2

18.9

1962

1.7

5.8

1.4

1.2

10.1

1963

2.5

3.1

0.6

0.7

6.9

1964

1.6

1.1

0.5

0.6

3.8

1965

2.1

1.8

0.5

0.6

5.0

1966

5.9

0.5

-

0.8

7.2

These drugs are on the Narcotic List in Sweden. Figures from
Narcotics Drug Committee Reports Iand
II (SOU 1967:25,41).

Large fluctuations were observed also during this period. A definite decrease was seen when it became known that a survey was being carried out. Nothing was mentioned in the press or otherwise, but the rumour spread among the buying clientele.

After the survey was completed a definite rise in the sales was observed. Thus the figures obtained are minimal figures.

During this period of 2 weeks a total of 9,888 cannulas, 306 glass syringes and 3,628 disposable plastic syringes were sold on a total of 2,254 occasions. These figures when corrected for one month, correspond to a total of 19,776 cannulas, 612 glass syringes and 7,256 disposable plastic syringes on 4,508 occasions.

On each occasion an average of 8 cannulas, 1-2 glass syringes and 5 disposable syringes were bought.

If the two periods, 1965 and 1966, are compared, with due consideration to the period of time covered, the number of cannulas sold has increased by 37 per cent, the number of glass syringes by 24 per cent and the number of disposable plastic syringes by 100 per cent.

The age distribution of the buyers is interesting to note. The results are given in table 21.

Not less than 26 per cent of the customers were 20 or under, or a total of 591; of these, 46 were 15 years or younger !

When looking at the various age groups the most frequent one was the age group 21-30 years (36%), followed by 16-20 years (24%), and 31-40 years (19%). The average age of all the customers was 29.9 years.

When analysing the buyers of the various types of syringes the buyers of disposable plastic syringes were younger, 27.4 years, against 31.5 years old in the group buying glass syringes.

As the number of out-patients, mainly diabetics and asthmatics, needing syringes and cannulas for legitimate use, has not essentially changed, the conclusion must be that these large sales of syringes and cannulas, especially of disposable plastic syringes, are due to the increasing proportion of drug abusers, who buy them for injecting the drugs. One more indication speaking in the same direction is the change to disposable syringes, which do not need to be sterilized, and have less risk of being broken when dropped, e.g. during the injection "ceremony" or afterwards during the peak effects of the drug.

While in 1965 the proportion of disposable syringes to glass syringes was 7 : 1, the proportion had risen in 1966 to 12 : 1. The same phenomenon is also reflected by the direct increase in sales; the sale of glass syringes increasing by 37 per cent and that of disposable syringes by 100 per cent.

TABLE 21

Sales of syringes and cannulas

Sales to single individuals recorded 7 - 21 October 1966 in all pharmacies and in the shops of the two largest surgical instrument firms in Sweden

Age groups

Type

-15

16-20

21-30

31-40

41-50

51-60

60-

Total

I Number of pieces

Cannulas

81

1433

3224

9238

1613

868

431

9888

Syringes:

Glass

7

71

100

7

27

25

5

306

Disposable

34

482

1099

1029

481

307

196

3628

II. Number of occasions

Cannulas

18

262

457

245

145

99

44

1270

Syringes:

Glass

4

43

60

50

19

20

4

200

Disposable

24

241

295

127

56

32

9

784

Total

46

546

802

422

220

151

57

2254

Percentage

2

24

36

19

10

7

2

100

Adapted from
Narcotics Drug Committee Report II (1967:41).

TABLE 22

Number of persons sentenced for violations of narcotics legislation, 1954-1965

Year

Stockholm

Göteborg

Malmö

Other cities

Urban areas

Total

1954

7

-

-

-

-

7

1955

1

2

-

-

-

3

1956

2

-

-

-

2

1957

2

-

-

-

-

2

1958

18

-

-

-

-

18

1959

48

2

-

-

-

50

1960

84

11

-

2

4

101

1961

109

7

1

2

4

123

1962

73

5

-

1

5

84

1963

73

6

-

1

6

86

1964

155

23

7

6

30

221

1965

141

86

8

23

60

318

Total

1954-1965

713

142

16

35

109

1015

From
Narcotics Drug Committee Report II (1967:41).

Another indication is the distribution of sales in the three largest cities. In 1966, 87 per cent of the sales occurred in Stockholm, 9 per cent in Göteborg and 4 per cent in Malmö.
[
1]

One phase of the drug abuse problem is reflected in the number of court sentences for violations of narcotics drug legislation. The results for the period 1954-1965 were reviewed by the Narcotics Drug Committee (1967:41); a detailed study, undertaken by I. Rexed, is in progress but some indications can be given here (1967:41).

During the early nineteen-fifties the number of cases of drug abuse was relatively low. This is reflected in the few cases tried for violations of regulations concerning narcotic drugs. During the four-year period 1954-1957 a total of 14 persons were tried and sentenced, or 2-7 persons per year. (See table 22, fig. 19.)

The sudden rise in the number of drug abusers in 1958 and in the number of violations of narcotics drug legislation and the desire to keep a close watch on the situation-most of the cases being concentrated in the Stockholm area - necessitated the prosecution of cases of violations to be assigned to one public prosecutor only.

The number of violations rose to 18 in 1958, 50 in 1959, 101 in 1960 and 123 in 1961. With the exception of a slight reduction in 1962 and 1963 the number has risen continuously, 318 cases being sentenced in 1965. The last figure represents a 50-100-fold increase in 10-12 years (table 22).

In the 12-year period studied a total of 1,015 cases were sentenced. These comprise a total of 845 persons, 78.5 per cent were men, and 21.5 per cent were women; out of these 125 were sentenced several times.

With regard to geographical distribution the Stockholm area was dominant, with 70 per cent of the total when considering the whole period, Göteborg had 14 per cent, Malmö 2 per cent only, and the rest was divided between other larger cities (3%) and smaller cities and rural areas (11%).

The picture is, however, changing. The proportion of cases in Stockholm is decreasing and that of other localities is increasing. In 1965 only 44 per cent of all sentences related to Stockholm. Göteborg had now 27 per cent of the total, Malmö 3 per cent, other larger cities 7 per cent and smaller cities and rural areas 19 per cent; a clear shift from the dominance of the capital, Stockholm, to other cities (table 22).

An analysis of the various types of violations has been carried out on the 149 cases in 1964-65, involving only one type of violation. The majority, or 67 per cent (101/149), were sentenced for illegal possession of narcotics, the rest for smuggling (25%) or for illicit trade (7%).

Fig. 19. Number of sentences for violations of narcotics drug legislation in Sweden, 1954-1965.

The remaining 390 cases for 1964-65 involved combined violations of various kinds, the majority of offences being illicit trade in narcotic drugs.

A total of 120 sentences in 1964-65, or 22 per cent (120/539) concerned smuggling.

With regard to the
drugs abused, central stimulants were involved in 84 per cent of the cases in 1964-65 (452/539), cannabis in 11 per cent, and opiates in 5 per cent only.

A special study was carried out on the material from Stockholm to find the reasons for not prosecuting a case. The prosecution was dropped in 14 per cent of the total number of cases tried in Stockholm in 1964 (25/180); this figure rose to 27 per cent in 1965 (52/193). In the majority of these cases (89 %), the original violation of narcotics drug legislation was only illegal possession. Thus in an increasing number of cases a prosecution for illegal possession of drugs on the National Narcotics List, especially when only small quantities were found, was not made unless this violation was accompanied by other types of violation.

The violations by physicians of legislation concerning narcotic drugs have mainly concerned unlawful prescription of narcotic drugs, abuse of narcotic drugs or a combination of both. Unlawful prescription may mean prescribing narcotic drugs to persons unknown to the physician (e.g. by telephone), or to persons whose identity has not been properly checked, or prescribing drugs in a way not in accordance with the present state of "scientific knowledge and proven professional experience," as the legal term is formulated.

The alleged violation is considered by the Disciplinary Council of the National Medical Board. Based on its findings the Board may dismiss the accusation, it may caution the physician or give a warning, revoke the right to prescribe narcotic drugs or restrict it to one pharmacy only, revoke the right to practise medicine, or recommend the case to the public prosecutor for court action.

A special study of all cases of violations of narcotic laws by physicians during the period 1957-1964 has been carried out for the Narcotics Drug Committee by Björnberg (SOU 1967:41, p. 174); some further analyses have been made for the present survey.

Number of cases

Out of a total of 3,393 cases handled by the Disciplinary Council during the eight-year period studied, 1957-1964, a total of 240, or 7.1 per cent, concerned violations of narcotics drug legislation. These 240 cases involved a total of 247 separate offences.

In table 23 the number of violations is given over the period of time studied. Three distinct periods can be discerned: 1957-60, 1961-62 and 1963-64.

1957-1960: The period was characterized by a low number of drug abusers in 1957, there was a sharp increase in 1958-59, two stimulant drugs - phenmetrazine and methylphenidate - were included in the National Narcotics Drug List in 1959, and a warning containing information on types of drugs abused was issued in 1960 by the National Medical Board to all physicians. These stages are reflected in the development in the situation among physicians.

In 1957-1959 the number of
violations of prescription rights among physicians was small, 8 per year on an average, but rose in 1960 to 17. The number of cases of
drug abuse among physicians, as such, or combined with violations of prescription rights, was 11 per year during this period; it showed a maximum in 1959 with 17 cases, then decreased again to 6 in 1960, in spite of the increase in prescription violations. (See table 23.)

1961-1962: During this period the abuse of stimulant drugs increased. The drugs were obtained mainly by diversion of legal prescriptions, in many cases asked for by telephone, the alleged patient not even appearing in person. In November 1962 the regulations were changed, strictly limiting the right to prescribe narcotic drugs by telephone. The work of police and public prosecutors was intensified to trace falsified prescriptions, and the physicians that might have been involved.

In this period the number of prescription
violations by physicians rose manifold, from 10-11 on an average in the period 1957-1960, to 49 to 61 in the period 1961-1962.

A special study of the
geographical site of violations showed that during this period the number of violations by physicians in smaller cities increased abruptly. This was due to the shift by the alleged patients from the now-warned physicians in the large cities, to those in smaller cities and in rural areas. At the end of the period the number of prescription violations fell again, due to the rural doctors also being warned.

The number of cases of
drug abuse in physicians was, however, low, and even tended to fall during the period.

1963-1964: Following the radical restrictions in 1962 in the right to prescribe narcotic drugs, the number of prescription
violations was small in 1963, then rose again in 1964, probably due to increased activity by police and public prosecutors to find cases of violations.

The number of cases of
drug abuse among physicians was still small, 4-5 per year, and seemed to be further reduced.

The average number of prescription
violations during the three periods studied, 1957-60, 1961-62 and 1963-64, was on an average 10, 55 and 15 per year, respectively.

The total, 182 cases over 8 years, corresponds to 23 per year, or, calculated on a total of 7,000 physicians in Sweden, to about 3 per 1,000 physicians. (See table 23.)

The number of cases of
drug abuse among physicians during these three periods, however, was 11, 6 and 4.5 per year, thus showing a significant decrease, a tendency which according to the impression from psychiatrists is still (1967) persisting. The figures quoted correspond to 1.6, 0.9 and 0.6 cases of drug abuse per 1,000 physicians.

Age

With regard to the age of the doctors involved (table 24) it was noticed that the average age among those violating prescription legislation was 56 years, the majority being 45-65 years. Not less than 24 per cent were over 65 years of age, thus retired, and only 5 per cent were below 36 years.

The mean age of the physicians abusing drugs was lower, 46.5, the majority being 36-55 years, only 5 per cent were older than 65 years, and 19 per cent were below 35 years.

Geographical localization

The greatest number of prescription violators were found in Stockholm, Göteborg and Malmö (102 cases), fewer in smaller cities (67) and very few in rural areas (13). (See table 25.)

When compared with the total number of physicians in these different localities - 1,800 physicians in Stockholm, 1,000 in Göteborg and Malmö, 3,400 in smaller cities and 800 in rural areas - the highest proportion of violators was seen in the large cities - 4.5 per 1,000 physicians per year, in smaller cities - 2.5 per 1,000 and in rural areas - 2.0 per 1,000.

With regard to
drug abuse among physicians the highest number was found in Stockholm (24 cases), there were 23 in smaller cities, 11 in rural areas and 7 in Göteborg and Malmö.

When relating these figures to the total number of physicians in these localities, the highest relative proportions of drug abuse were found in rural areas - 1.7 per 1,000 physicians per year and in Stockholm - 1.7 per 1,000 per year, twice as many as in other cities; in other large cities the figure was 0.7 per 1,000, and in small cities 0.9 per 1,000. (See table 25.)

Sex distribution

The proportion of prescription
violations was somewhat greater among men - 164 on 6,000 male physicians in 8 years, or 3.4 per 1000 per year - than among women, 18 per 1,000 female physicians in 8 years, or 2.3 per 1,000 per year, whereas the proportion of cases of drug abuse among physicians (61 men) was more than twice as large - 1.3 per 1,000 per year - than among women - 4 cases or 0.5 per 1,000 per year.

Among physicians attached to hospitals only a small proportion - 9 cases, or 5 per cent of all violations - had been engaged in prescription
violations, the majority of violations, 136 or 75 per cent, being committed by private practitioners, the rest or 37 in number by municipally or state-engaged "district" physicians. (See table 26.)

When referring the number of prescription violators to the actual numbers of physicians in each category - 3,200 attached to hospitals, 2,500 being private practitioners and 800 engaged as "district" doctors by the state or municipality - the under-representation of hospital physicians was still more accentuated- 0.4 per 1,000 per year, against 6.8 per 1,000 among private practitioners and 5.8 per 1,000 among district doctors.

When considering
drug abuse among physicians the hospital-attached physicians (24 cases) and private practitioners (27) were equally represented, while the municipal and state doctors had fewer cases (14). (See table 26.)

When considering the number of abusers in proportion to the total number of physicians within each category, the highest proportion of abuse was, however, seen among municipal or state-engaged doctors - 2.2 per 1,000 per year, than among private practitioners - 1.4 per 1,000, and the smallest among hospital physicians - 0.9 per 1,000. (See table 26.)

The age distribution is given in table 27, showing the hospital physicians being the youngest, around 40 years of age, and the private practitioners the oldest, around 57 years, with a high percentage of physicians of 65 years of age.

Opiates were the most frequent ones, prescribed in 60-70 per cent of the cases, both morphine derivatives and synthetic morphine-like drugs (e.g. dextromoramide, pethidine and methadone), and stimulant drugs in 30-40 per cent, the figures varying according to whether the number of prescriptions, or the number of cases, are used as the basis for the calculation.

Types of drugs abused

When considering the types of drugs abused, it was noted that 60 per cent of the physicians abused opiates, divided between morphine derivatives (56 per cent) and synthetic drugs (44 per cent). About 35 per cent abused stimulant drugs, and 5 per cent combined the two types.

Disciplinary measures

With regard to the disciplinary measures taken, partial "delegitimation" (revocation of the right to pres- cribe narcotic drugs) was applied in 29 per cent of the cases of prescription
violation, 3 per cent were referred to court procedure, other measures were taken in 41 per cent of the cases, e.g. issuing a warning; no measures were taken in 27 per cent.

In the cases of drug
abuse the revocation of the right to practice medicine was the measure chosen in 14 per cent of the cases, partial revocation, i.e. no right or partial right to prescribe narcotic drugs, was used in 81 per cent, and court procedures were initiated in 5 per cent (combined with delegitimation in one case).

The patients obtaining the prescriptions

Most of the persons who had obtained the prescriptions were engaged in criminal activities, giving false identity, pretending to suffer from a disease, etc.

In order to obtain an insight into the connexion between violations of prescription and criminal activity among the individuals asking for the prescription an analysis was carried out of 101 cases referred to the National Medical Board by the police and/or prosecutors concerning physicians who had violated prescription legislation- 38 cases in 1961, 47 in 1962 and 16 in 1964.

Out of the physicians involved in 1961, 84 per cent were situated in the Stockholm-Göteborg area, only 13 per cent in other cities and 3 per cent in rural areas, whereas in 1962 and 1964 the illegal activity was concentrated in the smaller cities (62%) and rural areas (8 %), only 30 per cent being in the Stockholm-Göteborg area.

The number of alleged patients having applied for the prescriptions was, however, very low, only three in 1961, two in 1962 and three in 1964.

Opiates mainly of opiate-type drugs were asked for by these alleged patients, dextromoramide (Palfium) being the most popular in 1961-1962, with stimulant drugs coming into the picture later.

Some interesting points in this study of violations of narcotics drug legislation by physicians must be stressed, viz. (i) the number of prescription
violations seems now to be rather constant, after an initial period of low incidence and an intermediate period with a high incidence; (ii) the violations are seen in the highest proportion in the large cities and among private practitioners and municipally or state-engaged physicians; very few cases are noted among hospital-attached physicians; (iii) drug
abuse is seen in the highest proportion in rural areas and large cities and in about the same proportion among all three categories of physicians, with some over-representation of municipally or state-engaged physicians and private practitioners, and (iv) the number of drug abusers among physicians is steadily decreasing and has been reduced by half to two-thirds in a period of eight years.

Organization: Because in earlier years the illegal activity was rather insignificant - only few seizures being made, e.g. on board ships of opium intended for delivery in another country - no group specialized in narcotic drugs was organized within the police force. Parallel to the increase in 1958 in the number of drug abusers and in the illicit trade in narcotics, mainly of stimulant drugs, and occasionally of opiates, a special Police Narcotics Drug Group was set up within the State Police to cope with the problem. It was to work in close co-operation with the Municipal Police and with the public prosecutor specially assigned to take care of cases of drug abuse. After the incorporation in 1965 of the Municipal Police forces into one National Police Force, a National Police Narcotics Drug Commission was organized. Today a total of around 20 persons are engaged in this work, including smaller groups in Göteborg and Malmö; the personnel is increased for special assignments. A close co-operation exists with the Public Prosecutors and the Customs Office, and via Interpol and other agencies with various bodies abroad.

Illicit traffic: The main drugs in the illicit traffic are the stimulant drugs, the amphetamines being on the National Narcotics Drug List since 1944, phenmetrazine (e.g. Preludin) and methylphenidate (e.g. Ritalina) being on this List since 1959, and hallucinogens, (e.g. LSD) since 1966.

Opiates appeared earlier only occasionally, and then usually due to diversion of legally obtained drugs; today an increase in illicit trade in opiates and similar drugs is seen.

In the last few years there has been an increased illicit traffic in cannabis, mainly in the form of hashish; the first seizures of hashish with an admixture of opium have now been made. In the past, cannabis was insignificant in the illicit traffic.

Smuggling and "pushing" of narcotic drugs is executed by single individuals as well as by organized groups. Among the "pushers" there are quite a few drug abusers who sell some of the drug they have obtained and use the rest themselves. Others are "leaders" of drug groups (" joints ", "geggar-kvart "); they provide the premises and the drugs, but sometimes do not use drugs themselves. A third category are "pushers ", often also selling other goods, e.g. alcohol. The organized groups often have a central "agency" which provides the money, and covers several countries; agents travel to foreign countries to buy illegal drugs, and act as messengers, or employ special messengers to bring the drugs to Sweden. "Pushers ", "pedlars" or "dealers" are engaged locally to sell the contraband to customers, and the money needed for buying drugs is obtained by buying and selling stolen goods, among other methods of financing.

A large number of individuals are engaged in the illicit trade. At one time 260 "pushers " - all known to the police - were gathered in one single locality in Stockholm; many hundreds of pushers are active every single day in the city. This activity explains, among other factors, the high figures of drug-exposed persons, e.g. in the Stockholm area alone every third pupil in the ninth grade has been offered narcotic drugs.

The drugs are brought into the country illegally by different routes, being smuggled by car, by airplane or by boat. Tablets have been found in specially built caches in automobiles in the upholstery, inside spare tires, in the chassis, etc. They have been carried in belts or in brassieres on the body or inside plastic toys, or in plastic bags among the goods in suitcases, or have come on speed-boats or fishing boats.

The drugs have sometimes been "planted" in some other person's car, e.g. in the car of a girl friend or of a person that the "messenger" has met by chance, e.g. on the ferry from the Continent.

Besides drugs brought into Sweden by smuggling, clandestine manufacture of narcotic drugs has also taken place on several occasions. On one of these occasions the chemical firm, selling the "precursor" or starting material, became suspicious and notified the police because the man buying the material gave no good reason why he needed it. Sometimes the drugs are being smuggled into Sweden in bulk, to be made into tablets in clandestine shops; recently 4 kg of an amphetamine substance worth several million Swedish crowns was seized by the customs officials.

Seizures: The total number of seizures of narcotic drugs by the Narcotics Division of the National Police Force during the period 1 January 1965 - 31 March 1967 was 538. Stimulant drugs - dominated by Preludin - represented 82 per cent of all drugs, cannabis 15 per cent, opiates 2 per cent of the total, and hallucinogens (LSD) less than 1 per cent.

A study of the yearly trend shows an increase both in the number of individuals suspected of violation of narcotics laws, and in the number of tablets seized. In 1965 a total of 607 persons were suspected of such violations, and a total of 213,532 tablets of stimulant drugs were seized. In 1966 the figures had risen to 654 persons and 365,256 tablets. In 1967 during the period 1 January - 31 May the figures were 399 persons suspected and 352,019 tablets seized, corresponding to an estimated number for 1967 of around 1,000 persons suspected.

In November 1967, 306,000 tablets were found in storage in one place near the coast, smuggled in from abroad, bringing up the total for 1967 to over 1 million.

The men engaged in the illegal trade were seized the moment they arrived to fetch the tablets for distribution to customers in the country.

The National Police Narcotics Drug Commission, working in Stockholm and over the country, is handling about 60 per cent of all persons suspected and about 75-80 per cent of the seizures made; the rest is divided between Göteborg and Malmö.

The tendency for 1965-1966 may be taken to illustrate the seizures of two stimulant drugs, phenmetrazine and methylphenidate. (It is to be noted that phenmetrazine was forbidden in Sweden from December 1965.)

Between 3,000 and 60,000 tablets of phenmetrazine were seized in each quarter, with a maximum in June 1965, and a minimum in June 1966, varying between 9 and 50 seizures per quarter, the highest number of seizures was in December 1965 and the lowest in June 1966; the seizure in November 1967 of 306,000 tablets is the highest known.

The picture is different for methylphenidate. Between a few hundred and 8,000 tablets were taken in each quarter, divided into 12-19 seizures per quarter, the maximum in June 1966; in that month phenmetrazine seizures were at a minimum.

These figures are minimal figures and reflect the trend only.

It is known that there must be several thousand abusers of stimulant drugs in Stockholm alone, many of them taking up to 100-200-300 tablets a day - crushing the tablets for use in injection. On this basis it can be estimated that the influx of illegally procured tablets must be 50-100,000 tablets per day or even higher, representing 100,000-200,000 Sw.cr. per day.
*

Cost: The price of the drugs peddled is settled according to demand and availability; it is higher on week-ends, when little is available and the demand is greater, and is lower on work days, when larger stocks are available. The usual profit on a tablet, sold for about 2 Sw.cr. (40 US cents or 3 sh.), is 10-20 times the original price of the drug.

Corresponding prices are paid for ampoules of morphine, amphetamines etc., or for doses of hashish or marihuana. A single dose, depending on availability and demand, costs around 5-20 Sw.cr. (1-4 US dollars or 27-30 sh.) and this is to be multiplied by 5-10 to get the daily costs to an addict. A heavy drug abuser spends as much as 100-300 Sw.cr. (20-60 US dollars, or £7-20) per day to obtain his drug of choice.

Customs Office

The co-operation between the Police and the Customs officials has been very close. Customs work has increased in recent years, in spite of the principle that tourist activity and travelling should be encouraged as much as possible, and travellers should be bothered as little as possible by Customs procedures.

U.S.$1.00 = Sw. cr. 5

Lately, however, checks have been made on tourists coming in cars from countries where cannabis can be bought, or on flights or charter flights returning from countries where stimulant drugs, for example, have been easily available due to lack of national legislation, or lack of law enforcement.

During the period 1 January 1965-31 May 1967, a total of 78 seizures were made by Customs officers. In these cases, stimulant drugs were found in 80 per cent, cannabis in 19 per cent and opiates in 1 per cent.

The number of seizures has increased manifold in the last few months of 1967, e.g. three large ones within one week, comprising many kilos of drugs in bulk, and hundreds of thousands of tablets, corresponding to a value of many millions of crowns on the illicit market. These last seizures have led to the beginning of a disclosure of a more organized illicit trade, reaching across Swedish borders.

A very interesting experiment is now being tried out, viz. the use of special dogs - Schäferhunden, Boxers and Newfoundlanders - trained to find drugs in hidden places. A large number of dogs are now in training, conditioned on cannabis and on chemical substances like phenmetrazine. Some dogs have already demonstrated their ability, and the results seem to be very promising, the proportion of dogs being able to detect even small quantities of different drugs hidden away in various places has been surprisingly high.

These dogs are being used by the Police as well as by the Customs officials.

The different legislative approaches to the drug problem cannot be discussed at length in this survey, and only a few points will be mentioned.

The work of the Police and Customs officials is in many instances hampered by the fact that stimulant drugs - by far constituting the greatest problem of drug abuse in Sweden - are not considered narcotic drugs, and often are not even on prescription, in many of the countries where they can be bought. This means that in many instances Swedish authorities have met with very little co-operation from authorities in other countries, when trying to stop illicit trade by investigating a transaction deemed as criminal in Sweden, but which is considered legal in the country where the deal was made.

Two solutions may be suggested: (i) to change Swedish legislation to make "attempts" to violate narcotics drug regulations illegal. This will be of great help in the prevention of smuggling and illegal production. By making illegal not only the actual act, but also the preparation to commit the act, means will be obtained to intensify the work of the Police and Customs officials. Such a change in the law would cover, for example, the beginning of negotiations to buy drugs in a foreign country, or the buying of the chemical products necessary for the clandestine production of stimulant drugs or LSD; (ii) to increase the possibilities for close co-operation between countries by also having specific drugs with hallucinogenic or stimulant action covered by strict legislation in all countries.

These goals can be reached by several means, (
a) by strict national regulations in all countries concerned, e.g. hallucinogens not being sold at all, and stimulant drugs being restricted in their sale on prescription only, (
b) by these two categories of drugs being considered as narcotic or dangerous drugs by national legislation, and (
c) by these drugs being covered by international agreements, similar to the ones concerning narcotic drugs.

The rationale for these measures lies in the fact that the stimulant drugs, primarily the amphetamines - amphetamine, dexamphetamine and metamphetamine - , phenmetrazine and methylphenidate, have been proven to be dependence-producing, they are abused in many countries and constitute a risk to public health. The problem is grave in some countries, it is growing in others. With regard to the hallucinogens, a number of countries have already covered drugs of this group - mainly mescaline, psilocybin and LSD - by strict legislation.

It seems therefore to be of importance to make provisions for international control of these drugs, which are not covered at present by international conventions, that induce dependence, are abused and constitute a risk to public health; the stimulant drugs - amphetamines, phenmetrazine and methylphenidate - and hallucinogens - at present mescaline, LSD and psilocybin - are the types of drugs primarily to be considered.

As a basis for an analysis of the problem of drug abuse some of the factors involved in the emergence of drug dependence need to be examined, and an attempt made to analyze them from an epidemiological point of view with reference to the agent, the individual, and the environment, i.e. the drug, the drug user, and his milieu.

Within one and the same group of agents certain relationships between chemical structure and action have been found, where even small changes in the molecule may bring about large changes in effect.

The addition of one CH
3-group to morphine leads to codeine, which only rarely causes dependence and severe abuse, whereas the addition of two acetyl groups (CO CH
3) to the morphine molecule leads to heroin, showing a very high potency of dependence.

Addition of an allyl group (CH: CH
3) to the nitrogen in morphine leads to an antagonist - nalorphine - counteracting the effects of morphine e.g. its acute respiration-depressant effects, its quality of precipitating abstinence in morphine-dependent individuals, besides being analgesic but inducing hallucinations even in small doses.

Development of the antagonist idea in the benzomorphan series with a different radical on the nitrogen leads to a potent analgesic drug - pentazocine - with no hallucinatory activity and devoid of dependence-producing properties, but precipitating abstinence when administered to a morphine-dependent individual.

Another example is seen in the methorphan series, where the levo compound has strong analgesic and dependence-producing properties whereas the dextro compound has antitussive action and is devoid of analgesic and dependence-producing properties, and the allyl-compound is an antagonist.

The intensity of the dependence-producing properties thus varies, not only within the same family of chemical compounds but also between compounds with the same biological properties but with different structure, e.g. from heroin and morphine over codeine to dextropropoxyphene and pentazocine.

Most probably the same is also true in the series of stimulant drugs.

The experience in Sweden seems to indicate that phenmetrazine (e.g. Preludin) has the highest potency, and the greatest risk of psycho-toxic, acute and chronic effects (Rylander 1966). Amphetamines and methylphenidate (e.g. Ritalina) seem to show less dependence-producing and psycho-toxic effects than phenmetrazine. Many drug abusers have stated for example that a switch from phenmetrazine to methylphenidate did not satisfy the craving. They had to increase the dose, and still did not get the same "kick" out of the substitute drug. Opiate abusers state the same with regard to the difference in experience with morphine-like drugs.

Therefore it does not seem unlikely that new stimulant drugs might be found that would show a cleavage between the stimulant and appetite-suppressing properties on one hand and the dependence-producing properties on the other, thus having a low risk to public health, a development which is on its way with regard to the opiates.

With the diethylpropion derivatives and similar groups, that are used widely for appetite suppression, the cases of true dependence with abuse seem to be very few in relation to the large number of persons using the drug. The satisfying action of the diethylpropion derivatives experienced by abusers of dependence-producing types of drugs, e.g. of stimulants, seems to be too weak to induce them to use the diethylpropion derivatives as a substitute for a prolonged period of time (unpublished study).

Dose administered

The doses taken of various drugs play a decisive role for the emergence of dependence. In the case of the opiates, dependence seems to emerge soon after the repeated administration even of therapeutic doses. For most other types of drugs, from stimulants to hypnotics, sedatives and LSD the dosage has to surpass a certain level, e.g. 6-8 times the therapeutic dose, in order to induce or create a state that may lead to dependence.

The risk for the emergence of dependence and of psychotoxic reactions thus increases with the dose administered: the higher the dose, the larger the number of individuals becoming dependent, the more intense the dependence and the greater the risk for psychotoxic reactions.

Modes of administration and type of drug taken

One factor essential for the ensuing effect is the concentration of the drug reached in the blood. Oral intake gives lower levels of concentration, and thus lower effects due to slow absorption and passage through the liver with its detoxifying processes, before the drug reaches the target organs, e.g. in the central nervous system. Parenteral administration, e.g. by intravenous injection, leads to higher blood level concentration with peak effects of a much higher intensity, which in certain cases could not be attained by oral doses, even if the dose were to be increased many times. Hence intravenous administration substantially increases the risk for the emergence of dependence and of psycho-toxic reactions.

The type of drug taken also plays a role. With cannabis various preparations have a different content of active principles. Thus hashish, the type of cannabis preferred at present in Sweden, has a higher content of the active principles (the tetrahydrocannabinols) than marihuana, and thus also bears a greater inherent risk for causing dependence and psycho-toxic effects.

Intervals between administration

If the intervals between doses are large, i.e. the drug is taken only occasionally, the drug and its metabolites or breakdown products will be completely eliminated before the next dose is taken, and the organism will have had time to recover.

If the intervals are small, i.e. the doses are taken at short intervals, the drug and/or its metabolites will not be completely eliminated from the body when the new dose is taken. This will lead to the new dose having an increased effect, the blood level will increase, and it will take longer until all of the drug has left the body. If the doses are taken with short intervals for a prolonged period of time, the effects will add up, a cumulative effect will arise, and the risk of psycho-toxic effects will be greatly increased.

Duration of drug use

The duration of drug use is another factor of importance. If a drug is taken only for a short period of time the risk of emergence of drug dependence and psychotoxicity is relatively small. If the drug is taken during a long period of time the risk is greater and increases with the duration of drug intake.

The critical time for emergence of drug dependence varies among other things with the type of drug abused. It is very short for most opiates, a matter of days to weeks. It is longer, usually a matter of weeks to months, for most stimulant drugs, hypnotics and sedatives; the period is much longer for alcohol, months to years, the average time for emergence of alcoholism being 6-12 years.

Increase in tolerance and dose

One of the mechanisms of adaptation to the effects of a drug is the emergence of tolerance, i.e. a diminished reaction to a standard dose on repeated administration.

Tolerance may be of a metabolic-enzymatic nature, the body being able to dispose of larger amounts of the drug per time unit, or it may be connected with local changes in the central nervous system, leading to a changed - in this case a reduced - reaction or response, most probably by interference with enzyme mechanisms in local chemical transmittor systems, or via changes in the integrative processes in the CNS.

In many cases tolerance does not emerge for all types of responses. Thus the individual may become tolerant to some effects, e.g. the euphoric ones, but not to others. He increases the dose to obtain the same desired effects, e.g. the "kick ", but at the same time the risk of psycho-toxic reactions is increased in organs or systems that do not show the same degree of tolerance and adaptation.

In the case of opiates the increase in dose to overcome tolerance phenomena is well known. For stimulant drugs a high degree of tolerance is seen. Many of the abusers injecting phenmetrazine for example, use daily doses of 50-100-200 tablets of 25 mg, corresponding to 750-5,000 mg daily, against the therapeutic dose of 2-3 tablets, i.e. 50-75 mg per day.

Untoward effects-psycho-toxicity

The use of various drugs may, depending on the type of drug, dosage, mode of administration, duration of intake etc. lead to acute and/or chronic untoward effects, beside drug dependence, here summarized in the term psycho-toxicity. Some principal viewpoints only will be given in this survey.

The acute effects may range from psychic disturbances, confusion, hallucinations and mental derangement to somatic disturbances of circulation and respiration, necessitating intensive expert treatment. Accidental death is not uncommon, e.g. after an overdosage resulting from taking a certain dose of a drug by injection instead of orally, or injecting a dose of a preparation with a higher content of active ingredients than expected.

The chronic effects may range from a series of somatic effects, among others depending on the type of drug taken, to more or less long-lasting psychic disturbances, e.g. for stimulant drugs going from a state of agitation, anxiety and confusion to hallucinations, depersonalization and paranoia, even aggression and even homicidal attempts have been observed, as well as suicidal attempts and suicides.

Risk with therapeutic use

With the exception of the opiates, where in most cases - terminal cancer patients and similar cases being excluded - only short-term therapy should be instituted, many of the other types of drugs can be used for a certain period of time if the patient is controlled and the dose kept at a minimum, within the limits recommended for ordinary therapeutic use. An increase in dose, together with an extension in time of the medication, increases the risk of emergence of dependence and of the appearance of psycho-toxic reactions.

In the case of some drugs, e.g. heroin in most countries, phenmetrazine in Sweden, and certain others, the risks are so high in relation to the therapeutic gains, and other drugs with equal potentiality in the therapeutic situation and giving lesser untoward effects are available, that these drugs have been dropped from therapeutic use. In Sweden they are excluded from the list of accepted remedies, heroin after the WHO recommendation of 1953, and phenmetrazine since December 1965.

The constitution and personality structure of the individual taking the drug, whether it be inborn and of genetic origin, or acquired, plays a definite role. Constitution in this context would imply all the mechanisms involved in the handling of the drug of an enzymatic nature, transmitter mechanisms, metabolic pathways, etc., and the mechanisms and target areas responding to the effects of the drug, mainly in the central nervous system. As one example it can be mentioned that when the rate of metabolism of the drug is high, due to a high amount of enzyme available or a peculiarity in the metabolic pathways, the drug is rapidly eliminated, and the risk of long-lasting effects is small, if the dose is kept constant. The rapid disappearance of the drug may induce the individual to take higher doses which may have a deleterious effect on certain target organs, and increase the risk of chronic damage.

If the rate of metabolism of the drug is low, and the dose is not adjusted properly, the risk is increased of the appearance of psycho-toxic effects.

The psychic make-up is also of importance. A neurotic personality increases the risk of emergence of psychotoxic effects and dependence. The same is true with regard to certain latent or manifest cerebral injuries, which also increase the risk of severe reactions, including the appearance of drug dependence and psycho-toxic effects.

This problem of the possible relationship between the personality of the user, and the effect of an agent is now recognized as of increasing importance. It helps to explain why a certain drug, e.g. phenmetrazine, may choose one effect in one individual, e.g. produce appetite suppression and only malaise, nausea, vomiting and headache on increase in dose, and no desire to go on taking the drug, while the same drug in another individual may induce stimulation, a feeling of being "high ", of elation and flight from reality, and awake the desire in him to go on taking the drug to renew these pleasurable sensations. Personality differences are to a certain extent responsible for the various ways in which the individual will react to the drug in different environments and in different situations.

An important part of the problem is therefore to evaluate what role differences in personality structure play in this respect, and to find out whether these structural elements are inborn or acquired, whether they can be diagnostisized among all the factors involved, and whether they can be prevented from coming into play.

An integral part of an analysis of causal relationships with regard to drug abuse and drug dependence must be devoted to the importance of environmental factors.

These are of various kinds. The type of home, the parental situation (parents living together or separated, a foster home), the school and the job, friends, gangs, and "sub-cultural" groups, all play a role. The rituals around the use, availability of premises for drug abuse, e.g. a drug-joint (" geggar-kvart "), the type and personality of the leader in the group, and the attitudes of parents, schools and employers, and the rituals, mores and conventions of the "sub-group" similarly affect the phenomenon of drug abuse.

Spread of habit and sources of contamination

The role of the epidemic spread of drug abuse, from a leader to members of the group, from an active drug abuser to his fiancée or other close friends - so-called satellite cases who share the drug available with the primary abuser - has already been stressed as part of various contributory social phenomena.

It is of importance from an epidemiological point of view to know in detail this mechanism of transfer of a habit, from person to person, from one group of individuals to another, as well as the exact links in the chain of the illicit trade in drugs, in order to be able to deal with the problem, to break the transfer chain, whether of the habit itself, or of the drug, at the crucial, and from a preventive point of view, most effective points.

Availability of the drug

One other point of importance is the availability of the drug of abuse. The availability depends on a number of different factors. It is the end-product of an interrelationship between the effects of legislation, including the possibilities to enforce the law by the activity of police and customs, of the availability by diversion of legal supplies, including prescriptions, or through illegal channels, the price in relation to the money available, the number of pushers and pedlars and the intensity and possibilities of the illicit trade - all these factors together determine availability.

Degree of social damage and risk to public health

The last factor to be discussed, and the most difficult one to evaluate, is the degree of social damage caused by the use, or abuse, of a drug by various groups within society and the risk to public health.

Essentially, the elements have to be weighed on a knowledge of medical consequences for the health of the individual, and of the social consequences for various strata of the population, e.g. in juveniles, and among certain groups, and the interference of the use with social functions. Details have been given in the present survey under chapters II, III and V-VII.

Based on the studies reviewed (chapters II-VII), the differences observed in the dynamics of the development before and after 1955 (respectively presented in I and II-VII above), the various types of drugs abused, the number of individuals involved and the various groups engaged in drug abuse an attempt will now be made to characterize the present state of drug abuse in Sweden, to summarize the findings and to point to some essential elements in the interplay between drug, individual and environment.

Before 1955, opiates - opium, morphine, morphine derivatives and synthetic morphine-like drugs - dominated the picture, comprising 77 per cent of the drugs abused, the rest, 23 per cent being stimulant drugs, or a total of 36 cases (Lindgren 1956). Already during the early fifties, however, an increasing abuse of stimulant drugs was noticed, but quantitatively it was still of a moderate proportion. Abuse of hypnotics and sedative drugs existed; the number of abusers was unknown; the number of suicides with these drugs was known, but not the proportion of chronic abusers.

The last decade has been characterized by the abuse of new types of drugs, at least new on the Swedish scene. On one hand the centrally acting stimulant drugs - phenmetrazine (e.g. Preludin) and methylphenidate (e.g. Ritalina), were introduced in 1958-1959, and on the other cannabis preparations, mainly hashish and to some extent also marihuana, entered the picture around 1962-1964; recently hallucinogens, mainly LSD, beginning with single cases in 1965 and now increasing in number has appeared. Finally, inhalation of volatile agents (" sniffing "), e.g. of glue, trichlorethylene or thinners, has become quite a problem among teen-agers, a problem that seems now to be decreasing.

The preference for one or the other type of drug has not only changed with time, but also with the group of individuals concerned, as well as with age.

Sniffing of volatile agents and cannabis smoking dominate in the young age-groups, mainly among teenagers, whereas injection of stimulant agents dominates the next age decade, 20-30 years, and spreads out both to younger and to older age groups. In older groups the hypnotic and sedative drugs dominate the abuse pattern, opiates still being abused today, but by a minority only, and mainly by those around 40 or over. Hallucinogens of the LSD type are beginning to be abused by an increasing number, starting already in the teen-age group. These hallucinogens have also been noticed in some individuals in the age groups 20-40 years. Hypnotics, sedative and tranquillizing agents, taken orally, dominate patients in hospital whereas injection of stimulant drugs dominates among individuals engaged in criminal activities.

The older drug abuse pattern was as a rule characterized by the individual abusing one type of drug only, e.g. opiates or hypnotics, or stimulant drugs.

Today it is typical that a substantial proportion, a fourth to one half, of the drug users combine different types of drugs. As examples it may be mentioned that a large proportion of opiate abusers - between 30 and 70 per cent of the sub-groups studied - also inject stimulant drugs, that many abusers of stimulant drugs also use various hypnotic or sedative drugs, orally or by injection, in some cases even simultaneously mixing the drugs in the same syringe, or injecting them simultaneously in the two arms. The same is also true of some abusers of hypnotic drugs who also inject stimulant drugs; many marihuana smokers also abuse other drugs, a certain proportion, especially when older, combining the smoking with injection of stimulants.

The true proportion of combination of drug abuse with abuse of alcohol is not known in all details. Among male drug abusers treated in hospitals around 20-30 per cent had taken the drug in combination with heavy alcohol intake. Among a group of severely damaged alcoholics, confined to alcoholic institutions, around 15 per cent had also abused drugs.

With the exception of the few opiate abusers known, who injected the drug, the dominating mode of administration of drugs abused before 1955 was orally, as tablets, whence the colloquial term "tablet abuse ", whether of stimulants, hypnotics or sedative drugs.

Beginning around 1958 a new mode of administration of stimulant drugs became popular, viz. injection of stimulant drugs, mainly phenmetrazine (Preludin), after crushing the tablets, extracting the active principle with water, filtrating the product through cotton and injecting the extract intravenously.

As already shown injection dominates the picture with regard to abuse of stimulant drugs; in some sub-groups, e.g. up to 80 per cent, among the !persons who come to the notice of the Police, and up to 77 per cent in cases referred to the Children's Welfare Board, and almost 100 per cent in forensic psychiatric patients. Injection is also observed in connexion with abuse of hypnotics, sedative drugs and tranquillizers, mainly by the same category that injects stimulants.

Sniffing of industrially used volatile agents such as glue, trichlorethylene or thinners, has also become popular in the last 10-15 years, mainly among groups of teenagers, but it diminishes after 17-18 years of age; in a certain number of these cases sniffing changes over directly to cannabis smoking and/or to abuse of stimulant drugs.

Another facet in the modern picture of drug abuse is "spree use ", i.e. indulgence in drugs or other agents in large doses, but on single occasions only, not on a continuous basis.

This was especially the case with regard to inhalation - (" sniffing ") of industrially used volatile agents, such as glue, trichlorethylene (" tri ") and diluting agents for paints (" thinners "). In most cases sniffing was only indulged in on one single occasion, seldom more regularly, being confined to the younger teen-age groups, 12-15 years and usually abandoned at about the age of 17-18 years.

In rare cases the dependence on these agents was obvious from the compulsive nature of the intake and a delirium-tremens-like syndrome on abrupt withdrawal. Other complications were liver and kidney damage, in rare cases blood dyscrasias with leukopenia due to bone marrow injury caused by the benzene component in thinner.

In a number of these cases a transition is seen to other drugs, mainly marihuana smoking and/or injection of stimulant drugs, the type of agent often depending on the habits of the environment.

Spree use of other drugs is also seen, e.g. injection of whatever the individual may lay his hands on, from hypnotics and tranquillizing agents to spirits and wines, anti-influenza tablets, asthma remedies, etc.; for many individuals, especially when being part of a sub-group in a "drug-joint ", the playing with the syringe and the rituals connected with the act of injection are an integral part of the picture.

Some of the drugs abused during later years have led to complications that were not foreseen.

Dependence, both psychic and physical, including withdrawal abstinence phenomena, is well known after prolonged use and abuse of opiates, and has also been seen among the opiate abusers in Sweden. In the case of stimulant drugs it was generally assumed, however, at least among the lay public and the popular press, that their prolonged use was not "dangerous" because these drugs were only "habit-forming", not "addiction producing ", their use not being accompanied by abstinence symptoms when they were abruptly withdrawn.

The actual development, however, has shown a different picture. The intense psychic dependence on stimulant drugs, mainly phenmetrazine, is obvious in many individuals, on very high doses, 100-200 tablets per day, inducing them to obtain the drug at any cost, the effects experienced being described in terms of a high degree of excitement (" the kick "), ecstasy and a sense of satisfaction. Yet the intense exhaustion, prolonged sleep and other symptoms during the first few days after abrupt withdrawal in cases with high degree of dependence after intake of very large doses for a long period of time, can be interpreted as part of an abstinence syndrome, even if some of these symptoms are, as far as we can judge today, an intensification of physiological changes. The abstinence syndrome concept is moreover supported by a series of tentative experiments on catecholamine metabolism, showing changes also during the withdrawal stage (pers. comm.).

Parallel to the widespread abuse of drugs among large segments of the population, the change-over to intravenous use and the increase in intensity of abuse with increase in the doses, there was an increase in the number and severity of complications.

Among the acute effects, usually brought about by injection of large doses - rarely after large oral doses - are shock and dizziness, with circulatory and respiratory disturbances or cardiac failure, sometimes transcendent loss of consciousness, and in severe cases accidental death due to overdosage. One mechanism is due to an individual not being used to drug intake, thus with a low tolerance, who is given the same large dose orally or intravenously as that taken by an individual used to prolonged drug intake, and who has acquired a high degree of tolerance. Another mechanism is due to the combined effect of alcohol and CNS-depressant drugs, having a potentiating effect on the same functions, e.g. on respiration; alcohol + barbiturates or alcohol + morphine may be fatal without involving extremely large doses.

Infections as complications after intravenous administration of drugs are discussed at length (chapter III), from local infections to transferral of virus hepatitis, the number rapidly increasing, around 400-500 cases being estimated for 1967.

Among chronic changes after prolonged use of stimulant drugs, in some cases after amphetamines, but more often after phenmetrazine (Rylander 1966) long lasting psychic changes are seen. These consist of toxic psychoses, mental derangement, schizophrenic delusions with depersonalization, delirious states and as noticed lately paranoia, sometimes with aggressiveness towards supposed enemies, suicidal attempts, and even suicides.

One of the most obvious traits in the present picture of drug abuse is the involvement of younger and younger age groups.

Up to 1954 almost none or very few individuals below the age of 21 were found among drug abusers, whether of opiates or stimulant drugs; after 1958 the increasing proportion of younger age groups has been clearly demonstrated in a total of eleven studies reviewed in the present survey, the percentage of juveniles ranging from a few per cent in the hospital population to 44 per cent among viral hepatitis patients (see tables 17, 21). The proportion of younger age groups is increasing, exemplified by findings among arrested individuals (pers. comm. by Inghe); the proportion was 2 per cent in April 1965 but rose to 28 per cent in April 1967.

Because all experience shows the difference in impact on the individual when a drug is administered during the growing state, i.e. in children and teen-agers, as opposed to adults, this shift in the abuse population from adults only in the age group of about 40-50 years, to younger age groups and juveniles is of an immense importance. The spread to younger generations may very likely lead to a more rapid spreading of various forms of drug abuse in society, to a larger number of drug-dependent individuals - as against drug-abusing individuals with spree use who leave the drug after one or more attempts - and to a larger number of individuals severely injured somatically and psychically.

Ten to fiften years ago the few drug abusers seen were mainly from the medical professions (around 23 per cent of the known abusers) or patients (around 50 per cent) who had obtained the drugs as part of a medication, usually for chronic pain, which, however, had not been discontinued in proper time, because the prescribing physician was not aware of the dependence producing nature of the drug prescribed. When these patients were treated for their drug dependence they rarely relapsed because the initial motivation to suppress pain no longer existed, and the possible euphoric effects of the prolonged use of the drug had not been strong enough. Abusers of hypnotics and sedatives did exist though their number was not known.

Only a small part of the drug abusers chose these drugs to overcome difficulties in their adjustment to the environment, because they were neurotics, depressed patients or individuals with a deviant personality, sociopaths and others.

Today, however, different groups are involved. The cases in the medical profession (tables 23-27) are decreasing in number, as are therapeutic cases, and cases from other groups are increasing, partly juveniles who are curious to test the effects, partly individuals with a deviant personality, not confining their drug use to short-term "experimentation", but indulging in an often intensive and prolonged abuse, within an increasing proportion of individuals with a criminal background.

Part of the population at risk takes drugs to produce specific effects, the" kick ", a flight from reality, "expansion of the mind ", etc. The combination of the type of drug used, the doses taken, intravenous use, the personality structure and psychic make-up and the effect of the environment have led to states of drug dependence where even prolonged periods of abstinence from the drug, psychotherapy and other measures have not been sufficient to reduce the underlying urge to take the drug to obtain the desired sensations. The relapse rate is often rather high, especially in cases with a deviant personality.

Part of the new picture is the establishment of new patterns of life, a new philosophy, so-called new "sub-cultures ".

In old days the drug abuser was a single individual, being induced to drug taking as part of his being treated for a disease, the drug being taken mainly to overcome pain. Today drug abuse in many instances is part of a joint act, within a sub-group, the drugs being taken as part of a ritual, to achieve an elevation of mood, a flight from reality, carrying the individual from his usual environment to new surroundings filled by sensations which he tries to feel over and over again. Drug taking has taken the place of alcohol in many of these groups, because the drugs are said to bring about more intense feelings and sensations than the alcohol and do not leave an overt trace of identification. A teen-ager can go home without his parents knowing that he has taken a drug, a possible change in his behaviour being excused as his being sick, no smell betraying his secret.

The sub-group is usually built around an established drug user, usually a person injecting stimulant drugs, or around a leader not taking the drug himself. The leader provides the place where the group can gather. The place is called a " drug-joint " (" geggar-kvart ") and is often situated in an old house that is to be torn down within a short time, in slum areas or other derelict places. He provides the utensils, e.g. needle and syringe, often the same needle and syringe is used by all members of the group. Further he provides the drug, maybe the first time free, to get customers, later on for a high price, getting higher as the need becomes greater and the craving more intense. Money is procured in various ways, not unusually by prostitution, male and female, by theft, or by the abuser buying the drug illegally using part of it himself and selling the rest for profit. Finally, he often introduces the beginner to the first smoke or the first injection, demonstrating the technique including how to prepare the injection. The same pattern may be seen in some school classes, one boy having learnt the use from somebody else and he in his turn inducing others to join and to test the effects.

Probably around 100-150 such groups, each comprising some 5-10 members, exist in Stockholm, or a total of 400-600 persons. Many of them are concentrated in a certain area, the "morass ", the drug-taking here being mixed with prostitution, aggression (three murders within a short time) and criminality.

Another type of sub-culture or sub-group is represented by groups of intellectuals, or quasi-intellectuals, artists, students and others, indulging in drugs; in these groups, besides the illegal provision of the drugs abused, very little of criminality, aggression or obvious unsocial behaviour is seen.

Many juveniles move from country to country and stay for longer or shorter periods. They are sometimes caught and punished, in many countries with severe sentences for illegal drug activity often including long prison sentences of up to 10-20 years. Others escape the penalty and move on to friendlier countries, or return home. Yet others are trapped by international gangs, engaged in drug traffic and often caught in this activity when passing a frontier, or, e.g. when involved in a road accident when the police may find the drugs hidden in the car.

Whether the total number of abusers is 5,000 or 7,000 which are figures mentioned, it is obvious that drug abuse in Sweden constitutes a public health problem, involving juveniles and other age groups in an increasing proportion, leading in a number of cases to severe acute and chronic ill-effects, and interfering with a number of social functions, thus constituting an obvious risk to public health.